DOSE Trial of Opioid Sparing Effect

• Status: Terminated
• Trial end date: 2020-11-06
• Target enrollment: 0
• Participant gender: All

Summary

Multicenter, double blind randomized controlled trial of fentanyl vs. fentanyl + dexmedetomidine as the initial regimen for maintenance of sedation in mechanically-ventilated, critically ill children.

This trial will evaluate the opioid-sparing effect of dexmedetomidine when administered with fentanyl to mechanically ventilated, critically ill children. Study drug or placebo will be administered with fentanyl, which will be titrated to achieve sedation scores consistent with response to light touch. Plasma samples and bedside assessments for pain, sedation, and delirium will be collected.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Duke University
• Collaborators: Intermountain Health Care, Inc.; Johns Hopkins University; National Institutes of Health (NIH); Vanderbilt University Medical Center
• Treatments: Dexmedetomidine; Fentanyl

Criteria

Inclusion Criteria:

1. Ages 0 to <18 years at the time of enrollment.

2. If < 6 months postnatal age, gestational age ≥ 35 weeks.

3. Admitted to an intensive care unit.

4. Planned or anticipated mechanically ventilation for ≥2 days.

5. Require sedation to maintain mechanical ventilation per clinical judgment.

6. No contraindication to receipt of fentanyl or dexmedetomidine per clinician judgment.

7. Availability and willingness of the parent/legal guardian to provide written informed consent.

Exclusion Criteria:

1. Previous participation in this study.

2. Severe traumatic brain injury as the underlying etiology for critical illness requiring mechanical ventilation or baseline pediatric cerebral performance category (PCPC) >3.

3. Planned receipt of sedatives other than fentanyl or dexmedetomidine.

4. Anticipated receipt of neuromuscular blockade for >48 consecutive hours during the study period.

5. Receipt of fentanyl or dexmedetomidine via continuous infusion for >12 hours in the 24 hours prior to enrollment.

6. Extracorporeal life support (including renal replacement therapy, extracorporeal membrane oxygenation, ventricular assist device, etc.) at the time of enrollment.

7. Chronic use of or recent overdose of serotonergic agents (selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase (MAO) inhibitors, cyclic antidepressants)

8. Known pregnancy

9. Known liver dysfunction, defined as: aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2x the upper limit of normal for age

10. Known or impending renal failure defined as: anuria > or equal to 12 hours prior to enrollment or requiring renal replacement therapy

11. High risk children, define as: a. known heart block b. known bradyarrythmia including clinically significant bradycardia (defined as requiring chronotropic agents or cardiac pacing to treat)

12. Receipt of mechanical ventilation during an admission for cardiac surgery

Note: receipt of drugs other than fentanyl or dexmedetomidine for intubation, and receipt of neuromuscular blockage for intubation, will not be considered exclusionary criteria.